Nabilone

Targets (2)

Identification

Name

Nabilone

Accession Number

DB00486 (APRD01127)

Type

Small Molecule

Groups

Approved, Investigational

Description

Nabilone is a synthetic cannabinoid with therapeutic use as an antiemetic and as an adjunct analgesic for neuropathic pain. It is a synthetic cannabinoid, which mimics the main ingredient of marijuana (THC) but it has more predictable side effects and causes no or minimal euphoria. Nabilone is not derived from the cannabis plant as is dronabinol.

In Canada, the United States, the United Kingdom and Mexico, nabilone is marketed as Cesamet. It was approved in 1985 by the United States FDA for treatment of chemotherapy-induced nausea and vomiting that has not responded to conventional antiemetics. Though it was approved by the FDA in 1985, the drug only began marketing in the United States in 2006. It is also approved for use in treatment of anorexia and weight loss in patients with AIDS.

Although it doesn't have the official indication (except in Mexico), nabilone is widely used as an adjunct therapy for chronic pain management. Numerous trials and case studies have demonstrate various benefits for condition such as fibromyalgia and multiple scerosis.

Nabilone is a racemate consisting of the (S,S) and the (R,R) isomers ("trans").

Nabilone is a cannabinoid with therapeutic uses. It is an analog of dronabinol (also known as tetrahydrocannabinol or THC), the psychoactive ingredient in cannabis. It is reserved for use in individuals who do not respond to the more commonly used anti-emetics. This is mainly because cannabinoids have potential adverse effects similar to that of cannabis and may cause changes in mood and behaviour.

Mechanism of action

The mode of action of nabilone has been studied in cats and dogs. Although its anti-emetic action is not yet fully understood, it is apparent that there are a number of points in the control systems of the body at which Nabilone could block the emetic mechanism. It is likely that nabilone exerts its actions via binding to the cannabinoid receptors.

Rapidly absorbed from the gastrointestinal tract following oral administration.

Volume of distribution

12.5 L/kg

Protein binding

Not Available

Metabolism

Hepatic. Two metabolic pathways have been suggested. The major pathway probably involves the direct oxidation of Nabilone to produce hydroxylic and carboxylic analogues. These compounds are thought to account for the remaining plasma radioactivity when carbinol metabolites have been extracted.

Route of elimination

The route and rate of the elimination of nabilone and its metabolites are similar to those observed with other cannabinoids, including delta-9-THC (dronabinol). Therefore, it appears that the major excretory pathway is the biliary system.

Half life

2 hours, with metabolites around 35 hours.

Clearance

Not Available

Toxicity

Symptoms of overdose include difficulty in breathing, hallucinations, mental changes (severe), nervousness or anxiety (severe). Monkeys treated with Nabilone at doses as high as 2mg/kg/day for a year experienced no significant adverse events. This result contrasts with the finding in a planned 1-year dog study that was prematurely terminated because of deaths associated with convulsions in dogs receiving as little as 0.5mg/kg/day. The earliest deaths, however, occurred at 56 days in dogs receiving 2mg/kg/day. The unusual vulnerability of the dog is not understood; it is hypothesised, however, that the explanation lies in the fact that the dog differs markedly from other species (including humans) in its metabolism of Nabilone.

Taxonomy

Description

This compound belongs to the class of organic compounds known as naphthopyranones. These are compounds containing a naphthopyran skeleton where a ring carbon bears a carboxylic acid group. Naphthtopyran is made up of the pyran ring fused to a naphthalene ring system.